SUMMARY Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent and heritable neurodevelopmental disorder. Neuroimaging studies have found that ADHD is associated with decreased volume of cortical and subcortical structures, delayed posterior to anterior cortical maturation, and dysfunction of fronto-striatal and thalamo- cortical networks. However, findings from these existing studies are highly inconsistent in terms of the structural and functional abnormality patterns. Beyond possible demographic and developmental factors, etiological heterogeneity of the disorder can be a significant component that contributes to the inconsistence of these findings. Among the complicated biological and environmental elements, familial heredity is the most significant factor for the emergence of ADHD. Relative to that in non-familial ADHD (ADHD-n), familial ADHD (ADHD-f) showed more severe executive dysfunction and much higher rate for persisting ADHD symptoms into adulthood. These findings suggest that ADHD-f may represent a biologically more homogeneous subgroup. However, neural substrates of familial vs. non-familial ADHD have not yet been well investigated. By utilizing advanced neuroimaging and analytic techniques, this research will assess the [parental history- related] familial risk influences on functional and structural brain organizations in children with ADHD. Two groups of ADHD (ADHD-f and ADHD-n)) and group-matched control children (TDC) will be involved. Based on extensive findings from existing neuroimaging and clinical studies conducted in our group and other groups, our general hypothesis is that compared to the TDC, both ADHD groups will show significant functional and structural alterations in frontal lobe and thalamus; while relative to ADHD-n, the ADHD-f group will show more severe functional and structural aberrance in frontal lobe and related circuitry. Our ultimate goal is to translate hypothesis-driven neurobiological correlates of the risk factors into clinically applicable biomarkers for guiding individualized interventions in ADHD. The findings of this research represent an important first step in the development of novel and refined intervention strategies for biologically homogeneous subgroups of ADHD. [This project will significantly enhance the research infrastructure and student education at the New Jersey Institute of Technology (NJIT), by providing biomedical and behavioral science-related training and research experiences to undergraduate and graduate students, especially underrepresented minorities and females. This would allow them to acquire a broad spectrum of fundamental and advanced knowledge and skills in all clinical and technical aspects involved in human subject clinical and neuroimaging research, and develop a vast network of collaborations through the active biomedical and clinical scientists involved in this project. This AREA project thus has significant positive impact on academics and research at NJIT.]